Bioactive Catalytic Nanocompartments Integrated into Cell Physiology and Their Amplification of a Native Signaling Cascade

Abstract

Bioactive nanomaterials have the potential to overcome the limitations of classical pharmacological approaches by taking advantage of native pathways to influence cell behavior, interacting with them and eliciting responses. Herein, we propose a cascade system mediated by two catalytic nanocompartments (CNC) with biological activity. Activated by nitric oxide (NO) produced by inducible nitric oxidase synthase (iNOS), soluble guanylyl cyclase (sGC) produces cyclic guanosine monophosphate (cGMP), a second messenger that modulates a broad range of physiological functions. As alterations in cGMP signaling are implicated in a multitude of pathologies, its signaling cascade represents a viable target for therapeutic intervention. Following along this line, we encapsulated iNOS and sGC in two separate polymeric compartments that function in unison to produce NO and cGMP. Their action was tested <i>in vitro</i> by monitoring the derived changes in cytoplasmic calcium concentrations of HeLa and differentiated C2C12 myocytes, where the produced second messenger influenced the cellular homeostasis.